rs78564552
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_016302.4(CRBN):c.88G>A(p.Glu30Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00344 in 1,610,774 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0035 ( 13 hom. )
Consequence
CRBN
NM_016302.4 missense
NM_016302.4 missense
Scores
1
5
7
Clinical Significance
Conservation
PhyloP100: 7.16
Genes affected
CRBN (HGNC:30185): (cereblon) This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found in the cytoplasm localized with a calcium channel membrane protein, and is thought to play a role in brain development. Mutations in this gene are associated with autosomal recessive nonsyndromic cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0070037544).
BP6
?
Variant 3-3175249-C-T is Benign according to our data. Variant chr3-3175249-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210764.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00261 (396/151976) while in subpopulation NFE AF= 0.00471 (320/67950). AF 95% confidence interval is 0.00428. There are 0 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRBN | NM_016302.4 | c.88G>A | p.Glu30Lys | missense_variant | 2/11 | ENST00000231948.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRBN | ENST00000231948.9 | c.88G>A | p.Glu30Lys | missense_variant | 2/11 | 1 | NM_016302.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00261 AC: 396AN: 151860Hom.: 0 Cov.: 33
GnomAD3 genomes
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396
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GnomAD3 exomes AF: 0.00260 AC: 653AN: 251208Hom.: 3 AF XY: 0.00275 AC XY: 373AN XY: 135764
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GnomAD4 exome AF: 0.00352 AC: 5139AN: 1458798Hom.: 13 Cov.: 29 AF XY: 0.00352 AC XY: 2556AN XY: 725986
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GnomAD4 genome ? AF: 0.00261 AC: 396AN: 151976Hom.: 0 Cov.: 33 AF XY: 0.00244 AC XY: 181AN XY: 74280
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ExAC
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | CRBN: BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 12, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 29, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
0.18, 0.28
.;B;B
Vest4
0.21, 0.23
MVP
0.79
MPC
0.11
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at